{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:02:47Z","timestamp":1787666567559,"version":"build-2736575974"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>DNA methylation contributes to tumor formation, development and metastasis. Epigenetic dysregulation of stem cells is thought to predispose to malignant development. The clinical significance of DNA methylation in ovarian tumor-initiating cells (OTICs) remains unexplored. We analyzed the methylomic profiles of OTICs (CP70sps) and their derived progeny using a human methylation array. qRT\u2013PCR, quantitative methylation-specific PCR (qMSP) and pyrosequencing were used to verify gene expression and DNA methylation in cancer cell lines. The methylation status of genes was validated quantitatively in cancer tissues and correlated with clinicopathological factors. ATG4A and HIST1H2BN were hypomethylated in OTICs. Methylation analysis of ATG4A and HIST1H2BN by qMSP in 168 tissue samples from patients with ovarian cancer showed that HIST1H2BN methylation was a significant and independent predictor of progression-free survival (PFS) and overall survival (OS). Multivariate Cox regression analysis showed that patients with a low level of HIST1H2BN methylation had poor PFS (hazard ratio (HR), 4.5; 95% confidence interval (CI), 1.4\u201314.8) and OS (HR, 4.3; 95% CI, 1.3\u201314.0). Hypomethylation of both ATG4A and HIST1H2BN predicted a poor PFS (HR, 1.8; 95% CI, 1.0\u20133.6; median, 21 months) and OS (HR, 1.7; 95% CI, 1.0\u20133.0; median, 40 months). In an independent cohort of ovarian tumors, hypomethylation predicted early disease recurrence (HR, 1.7; 95% CI, 1.1\u20132.5) and death (HR, 1.4; 95% CI, 1.0\u20131.9). The demonstration that expression of ATG4A in cells increased their stem properties provided an indication of its biological function. Hypomethylation of ATG4A and HIST1H2BN in OTICs predicts a poor prognosis for ovarian cancer patients.<\/jats:p>","DOI":"10.1093\/hmg\/ddt583","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T02:46:39Z","timestamp":1385001999000},"page":"1894-1906","source":"Crossref","is-referenced-by-count":64,"title":["Hypomethylation signature of tumor-initiating cells predicts poor prognosis of ovarian cancer patients"],"prefix":"10.1093","volume":"23","author":[{"given":"Yu-Ping","family":"Liao","sequence":"first","affiliation":[{"name":"1 \u00a0Graduate Institute of Life Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"1 \u00a0Graduate Institute of Life Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Lan","family":"Huang","sequence":"additional","affiliation":[{"name":"4 \u00a0Department of Obstetrics and Gynecology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Hsuan","family":"Su","sequence":"additional","affiliation":[{"name":"4 \u00a0Department of Obstetrics and Gynecology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"6 \u00a0Department of Life Science, National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chang","family":"Chang","sequence":"additional","affiliation":[{"name":"3 \u00a0Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei 11490, Taiwan"},{"name":"7 \u00a0Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Hsien","family":"Yu","sequence":"additional","affiliation":[{"name":"3 \u00a0Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"8 \u00a0Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Shyen","family":"Yen","sequence":"additional","affiliation":[{"name":"8 \u00a0Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth P.","family":"Nephew","sequence":"additional","affiliation":[{"name":"9 \u00a0Medical Sciences Program,"},{"name":"10 \u00a0Indiana University Simon Cancer Center and"},{"name":"11 \u00a0Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"1 \u00a0Graduate Institute of Life Sciences and"},{"name":"2 \u00a0Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"3 \u00a0Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei 11490, Taiwan"},{"name":"4 \u00a0Department of Obstetrics and Gynecology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan"},{"name":"5 \u00a0School of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,11,20]]},"reference":[{"key":"2022050522052938700_DDT583C1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.20138","article-title":"Cancer statistics, 2012","volume":"62","author":"Siegel","year":"2012","journal-title":"CA Cancer J. 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